Protective Role of Apelin Against Cyclosporine-Induced Renal Tubular Injury in Rats

2017 ◽  
Vol 49 (6) ◽  
pp. 1499-1509 ◽  
Author(s):  
J.S. Kim ◽  
J.W. Yang ◽  
B.G. Han ◽  
H.J. Kwon ◽  
J.H. Kim ◽  
...  
Keyword(s):  
Protective Role ◽  
Tubular Injury ◽  
Renal Tubular

scholarly journals Protective Role of Vitamin D in Renal Tubulopathies

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 115 ◽  
Author(s):  
Guido Gembillo ◽  
Valeria Cernaro ◽  
Rossella Siligato ◽  
Francesco Curreri ◽  
Antonino Catalano ◽  
...  
Keyword(s):  
Vitamin D ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Tubular Injury ◽  
Dihydroxyvitamin D3 ◽  
Damage Response ◽  
Regulation Mechanisms ◽  
Renal Tubular ◽  
The Right

Vitamin D is tightly linked with renal tubular homeostasis: the mitochondria of proximal convoluted tubule cells are the production site of 1α,25-dihydroxyvitamin D3. Patients with renal impairment or tubular injury often suffer from chronic inflammation. This alteration comes from oxidative stress, acidosis, decreased clearance of inflammatory cytokines and stimulation of inflammatory factors. The challenge is to find the right formula for each patient to correctly modulate the landscape of treatment and preserve the essential functions of the organism without perturbating its homeostasis. The complexity of the counter-regulation mechanisms and the different axis involved in the Vitamin D equilibrium pose a major issue on Vitamin D as a potential effective anti-inflammatory drug. The therapeutic use of this compound should be able to inhibit the development of inflammation without interfering with normal homeostasis. Megalin-Cubilin-Amnionless and the FGF23-Klotho axis represent two Vitamin D-linked mechanisms that could modulate and ameliorate the damage response at the renal tubular level, balancing Vitamin D therapy with an effect potent enough to contrast the inflammatory cascades, but which avoids potential severe side effects.

scholarly journals Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Fei Zhao ◽  
Li-Xin Feng ◽  
Qian Liu ◽  
Hong-Shen Wang ◽  
Cheng-Yuan Tang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Quality Control ◽  
Kidney Injury ◽  
Protective Role ◽  
Mitochondrial Quality Control ◽  
Therapy Strategy ◽  
Nrf2 Signaling Pathway ◽  
Short And Long Term ◽  
Renal Tubular

Contrast-induced acute kidney injury (CI-AKI) is the third common cause of acute kidney injury (AKI), which is associated with poor short- and long-term outcomes. Currently, effective therapy strategy for CI-AKI remains lacking. Stanniocalcin-1 (STC1) is a conserved glycoprotein with antiapoptosis and anti-inflammatory functions, but the role of STC1 in controlling CI-AKI is unknown. Here, we demonstrated a protective role of STC1 in contrast-induced injury in cultured renal tubular epithelial cells and CI-AKI rat models. Recombinant human STC1 (rhSTC1) regulated mitochondrial quality control, thus suppressing contrast-induced mitochondrial damage, oxidative stress, inflammatory response, and apoptotic injury. Mechanistically, activation of the Nrf2 signaling pathway contributes critically to the renoprotective effect of STC1. Together, this study demonstrates a novel role of STC1 in preventing CI-AKI and reveals Nrf2 as a molecular target of STC1. Therefore, this study provides a promising preventive target for the treatment of CI-AKI.

scholarly journals Renal tubular injury induced by glyphosate combined with hard water: the role of cytosolic phospholipase A2

2021 ◽  
Vol 9 (2) ◽  
pp. 130-130
Author(s):  
Ruojing Wang ◽  
Jing Chen ◽  
Fan Ding ◽  
Lin Zhang ◽  
Xuan Wu ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Hard Water ◽  
Cytosolic Phospholipase A2 ◽  
Tubular Injury ◽  
Cytosolic Phospholipase ◽  
Renal Tubular

scholarly journals Role of p53/miR-155-5p/sirt1 loop in renal tubular injury of diabetic kidney disease

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Yue Wang ◽  
Zong-ji Zheng ◽  
Yi-jie Jia ◽  
Yan-lin Yang ◽  
Yao-ming Xue
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Tubular Injury ◽  
Diabetic Kidney ◽  
Renal Tubular

Abstract P544: Osteopontin Deficiency Decreases Autophagy and Exacerbates Tubular Injury in Acute Kidney Injury Induced by Folic Acid

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Tomoaki Nagao ◽  
Takafumi Okura ◽  
Akiko Tanino ◽  
Ken-ichi Miyoshi ◽  
Masayoshi Kukida ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Folic Acid ◽  
Kidney Injury ◽  
Immunohistochemical Analysis ◽  
Tubular Injury ◽  
Histological Changes ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Osteopontin (OPN), a secreted glycosylated phosphoprotein and pro-inflammatory cytokine, has been implicated in the pathology of several renal conditions, especially renal fibrosis in chronic kidney disease. OPN is slightly expressed in renal tubular cells in normal condition, but after acute tubular injury, OPN is highly induced in these cells. However, the role of induced OPN is still unclear. The aim of this study was to clarify the roles of OPN in acute kidney injury (AKI). AKI was induced in wild type (WT) and OPN knockout (KO) mice by using folic acid (FA) injection (0.35mg/kg). After 2days of injection, 34% of WT mice died, whereas 54% of KO died from renal failure. Kidneys from survived mice were removed and the renal histological changes, protein expression were examined. BUN and Creatinine levels were markedly elevated in WT-AKI and KO-AKI mice (BUN: WT-sham; 25.7±4.7mg/dl, WT-AKI; 315.0±173.2mg/dl, KO-AKI; 337.7±163.7mg/dl, Creatinine: WT-sham; 0.08±0.03 mg/dl, WT-AKI; 1.60±0.87 mg/dl, KO-AKI; 1.80±0.94 mg/dl). Renal OPN mRNA expression was increased in WT-AKI mice compared to WT-sham mice (p<0.05). High levels of OPN expression in renal tubular cells were induced in WT-AKI mice. TUNEL positive tubular cells were increased in KO-AKI mice compared to WT-AKI mice. In immunohistochemical analysis, Kidney injury molecules 1 (Kim-1) positive tubular cells were also highly increased in KO-AKI mice compared to WT-AKI mice. In contrast, LC3B (autophagy related protein) positive tubular cells were decreased in KO-AKI mice compared to WT-AKI mice. These results indicate that OPN deficiency exacerbates tubular injury via through the inhibiting autophagy in folic acid induced AKI mice.

scholarly journals zVAD-fmk prevents cisplatin-induced cleavage of autophagy proteins but impairs autophagic flux and worsens renal function

2012 ◽  
Vol 303 (8) ◽  
pp. F1239-F1250 ◽  
Author(s):  
Christian Herzog ◽  
Cheng Yang ◽  
Alexandrea Holmes ◽  
Gur P. Kaushal
Keyword(s):  
Renal Function ◽  
Therapeutic Agent ◽  
Kidney Injury ◽  
Protective Role ◽  
Autophagic Flux ◽  
Tubular Epithelial Cells ◽  
Cisplatin Nephrotoxicity ◽  
Autophagy Pathway ◽  
Renal Tubular

Cisplatin injury to renal tubular epithelial cells (RTEC) is accompanied by autophagy and caspase activation. However, autophagy gradually decreases during the course of cisplatin injury. The role of autophagy and the mechanism of its decrease during cisplatin injury are not well understood. This study demonstrated that autophagy proteins beclin-1, Atg5, and Atg12 were cleaved and degraded during the course of cisplatin injury in RTEC and the kidney. zVAD-fmk, a widely used pancaspase inhibitor, blocked cleavage of autophagy proteins suggesting that zVAD-fmk would promote the autophagy pathway. Unexpectedly, zVAD-fmk blocked clearance of the autophagosomal cargo, indicating lysosomal dysfunction. zVAD-fmk markedly inhibited cisplatin-induced lysosomal cathepsin B and calpain activities and therefore impaired autophagic flux. In a mouse model of cisplatin nephrotoxicity, zVAD-fmk impaired autophagic flux by blocking autophagosomal clearance as revealed by accumulation of key autophagic substrates p62 and LC3-II. Furthermore, zVAD-fmk worsened cisplatin-induced renal dysfunction. Chloroquine, a lysomotropic agent that is known to impair autophagic flux, also exacerbated cisplatin-induced decline in renal function. These findings demonstrate that impaired autophagic flux induced by zVAD-fmk or a lysomotropic agent worsened renal function in cisplatin acute kidney injury (AKI) and support a protective role of autophagy in AKI. These studies also highlight that the widely used antiapoptotic agent zVAD-fmk may be contraindicated as a therapeutic agent for preserving renal function in AKI.

scholarly journals BCL-XL is essential for the protection from secondary anemia caused by radiation-induced fatal kidney damage

2020 ◽  
Author(s):  
Kerstin Brinkmann ◽  
Paul Waring ◽  
Stefan Glaser ◽  
Verena Wimmer ◽  
Duong Nhu ◽  
...  
Keyword(s):  
Protective Role ◽  
Kidney Damage ◽  
Obstructive Nephropathy ◽  
Γ Irradiation ◽  
Adult Mice ◽  
Renal Tubular Epithelium ◽  
Adult Kidney ◽  
Total Body ◽  
Renal Tubular

AbstractStudies of gene-targeted mice identified the roles of the different pro-survival BCL-2 proteins during embryogenesis, but less is known about the roles of these proteins in adults, including in the response to cytotoxic stresses, such as treatment with anti-cancer agents. We investigated the role of BCL-XL in adult mice using a strategy where prior bone marrow transplantation allowed for loss of BCL-XL exclusively in non-hematopoietic tissues to prevent anemia caused by BCL-XL-deficiency in erythroid cells. Unexpectedly, the combination of total-body γ-irradiation (TBI) and genetic loss of Bcl-x caused secondary anemia resulting from chronic renal failure due to apoptosis of renal tubular epithelium with secondary obstructive nephropathy. These findings identify a critical protective role of BCL-XL in the adult kidney and inform on the use of BCL-XL inhibitors in combinations with DNA damage-inducing drugs for cancer therapy.SummaryThe inducible loss of BCL-XL in all cells of adult mice causes primary anemia due to apoptosis of erythroid and megakaryocytic cell populations. In contrast γ-radiation plus loss of BCL-XL in all cells except hematopoietic cells causes secondary anemia resulting from kidney damage.

Epigenetic mechanisms of nephroprotection in diabetic nephropathy: focus is on sirtuin-1

2021 ◽  
Vol 25 (6) ◽  
pp. 9-15
Author(s):  
K. A. Aitbaev ◽  
I. T. Murkamilov ◽  
V. V. Fomin ◽  
Zh. A. Murkamilova ◽  
F. A. Yusupov
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Diseases ◽  
Critical Role ◽  
Protective Role ◽  
Kidney Damage ◽  
Sirtuin 1 ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Nephroprotective Effect

Numerous studies have shown the critical role of sirtuin-1 deacetylase (SIRT1) in the protection of renal cells from endogenous and exogenous stresses. A protective role for SIRT1 has been established in both podocytes and renal tubular cells in many kidney diseases, including diabetic nephropathy (DN). SIRT1 has also been shown to have nephroprotective effects in DN, in part through the deacetylation of transcription factors involved in disease pathogenesis, such as p53, FOXO, RelA / p65NF-KB, STAT3, and PGC1a / PPARy. Recently, it was found that podocyte-specific overexpression of SIRT1 attenuates proteinuria and kidney damage in an experimental model of DN, suggesting the possibility of using SIRT1 as a potential target for the treatment of kidney disease. In addition, SIRT1 agonists such as resveratrol and BF175 have been shown to reduce diabetic kidney damage in several experimental animal models. It has also been shown that puerarin, a Chinese herbal medicine, activates SIRT1, providing nephroprotection in a mouse model of DN. In addition to SIRT1 agonists, inhibitors of bromodomain, in particular, MS417, also have a nephroprotective effect. These results suggest that SIRT1 agonists and bromodomain inhibitors may be new potential therapeutic agents that slow the progression of DN.

scholarly journals Circulating Mitochondrial DNA Stimulates Innate Immune Signaling Pathways to Mediate Acute Kidney Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaye Liu ◽  
Zhanjun Jia ◽  
Wei Gong
Keyword(s):  
Acute Kidney Injury ◽  
Mitochondrial Dna ◽  
Kidney Injury ◽  
Innate Immune ◽  
Tubular Injury ◽  
Comprehensive Overview ◽  
Molecular Pattern ◽  
Innate Immune Signaling ◽  
Renal Tubular

Mitochondrial dysfunction is increasingly considered as a critical contributor to the occurrence and progression of acute kidney injury (AKI). However, the mechanisms by which damaged mitochondria mediate AKI progression are multifactorial and complicated. Mitochondrial DNA (mtDNA) released from damaged mitochondria could serve as a danger-associated molecular pattern (DAMP) and activate the innate immune system through STING, TLR9, NLRP3, and some other adaptors, and further mediate tubular cell inflammation and apoptosis. Accumulating evidence has demonstrated the important role of circulating mtDNA and its related pathways in the progression of AKI, and regulating the proteins involved in these pathways may be an effective strategy to reduce renal tubular injury and alleviate AKI. Here, we aim to provide a comprehensive overview of recent studies on mtDNA-mediated renal pathological events to provide new insights in the setting of AKI.

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